It is proposed to develop a liquid chromatograph-mass spectrometer interface which will permit direct and continuous monitoring of the chromatographic effluent and which can be applied to biological molecules of extremely low volatility. The interface will employ laser vaporization and molecular beam techniques to insure minimal contamination of the mass spectrometer and interface chambers by solvent, involatile sample, and buffer molecules. Experiments will be carried out to establish sensitivity and to determine operating parameters for applications with different high-pressure liquid chromatographic separation techniques including partition, adsorption, gel permeation, and ion-exchange. A double crossed-beam ionizer is employed to provide both electron and chemical ionization mass spectra. After completion of the prototype instrument, tests will be conducted on components of nucleic acids, ranging from purine and pyrimidine bases to ogligonucleotide mixtures derived from transfer RNA.